Ex Parte Sigg et al

Patent Trial and Appeal Board

Jan 11, 2017

12722386 (P.T.A.B. Jan. 11, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/722,386 03/11/2010 Daniel C. Sigg P0034773.01(134.03410101) 3008
26813 7590 01/12/2017
MUETING, RAASCH & GEBHARDT, P.A.
P.O. BOX 581336
MINNEAPOLIS, MN 55458-1336
EXAMINER
OSINSKI, BRADLEY JAMES
ART UNIT PAPER NUMBER
3763
MAIL DATE DELIVERY MODE
01/12/2017 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DANIEL C. SIGG, DAVID SCHWARTZMAN,
EDUARDO N. WARMAN, RODOLPHE KATRA,
and SANJEEV G. SHROFF
Appeal 2015-002136
Application 12/722,386
Technology Center 3700
Before ERIC B. GRIMES, ULRIKE W. JENKS, and
ROBERT A. POLLOCK, Administrative Patent Judges.
POLLOCK, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal1 under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 1—4, 6—10, and 21—37. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
According to the Specification, “[hjeart failure can be classified as
heart failure with preserved ejection fraction (also referred to as diastolic
1 Appellants identify the Real Party in Interest as Medtronic, Inc. (App. Br.
3).
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Application 12/722,386
heart failure) or as heart failure with reduced ejection fraction (also referred
to as systolic heart failure).” Spec. 1:34—2:2. “Ejection fraction (EF) is the
percentage of blood pumped out of the left ventricle with each heartbeat.”
Id. at 1:29-30.
The Specification discloses “methods of treating heart disease with
the pericardial administration of an anti-fibrotic agent.” Id. at 2:14—15.
“[T]he methods . . . may be used for the treatment of heart failure with
preserved ejection fraction.” Id. at 6:28—29. Preferably, “the anti-fibrotic
agent is relaxin . . . [which] is a naturally occurring peptide hormone.” Id. at
7:24-27.
Claims 1 and 23 are representative of the claims on appeal and read as
follows:
1. A method of treating a subject with heart failure with
preserved ejection fraction, the method comprising:
the determination that a subject suffers from heart failure
with preserved ejection fraction, and
the pericardial administration of an anti-fibrotic agent to
the subject determined to suffer from heart failure with
preserved ejection fraction.
23. A method of treating a subject with heart failure with
preserved ejection fraction, the method comprising:
the determination that a subject suffers from heart failure
with preserved ejection fraction, and
the delivery of relaxin into the pericardial space of the
heart of the subject determined to suffer from heart failure with
preserved ejection fraction.
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Application 12/722,386
The Examiner has rejected claims 1—4, 6—10, and 21—37 under
35 U.S.C. § 103(a) as obvious in view of Samuel2 and Struijker-Boudier3
(Ans. 2-4).
The issues presented are: Does the evidence of record support the
Examiner’s conclusion that the combination of Samuel and Struijker-
Boudier would have made obvious a method of treating heart failure with
preserved ejection fraction by the pericardial administration of an anti-
fibrotic agent, as required by claim 1, or relaxin, as required by claim 23?
We have reviewed Appellants’ contentions that the Examiner erred in
rejecting claims 1—4, 6—10, and 21—37 as obvious over the cited art. App.
Br. 6—18, Reply Br. 1—6. We disagree with Appellants’ contentions and
adopt the findings concerning the scope and content of the prior art set forth
in the Examiner’s Answer and Final Rejection.4 For emphasis, we highlight
and address the following:
Findings of Fact
1. Samuel discloses
A method for treating cardiac fibrosis resulting from inj ury of a
mammalian heart. . . [which comprises] the step of cont acting a
therapeutically effecti ve amount of relaxin and/or an LGR7
activating agent with cardiac cells . . . in an amount sufficient to
reduce the fibrosis.
Samuel, Abstract. LGR7 “refers to a G protein-coupled receptor activated
by relaxin H2.” Id. 144.
2 Chrishan Surendran Samuel et al., US 2006/0264367 Al, Nov. 23, 2006.
3 Harry A.J. Struijker-Boudier et al., US 2003/0009145 Al, Jan. 9, 2003.
4 Office Action mailed Dec. 12, 2013.
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2. “Cardiac fibrosis is a hallmark of heart disease and ... is
characterized by a disproportionate accumulation of fibrillar collagen.” Id.
12. “The proximal effector cells in this process are fibroblasts, which when
activated to become myofibroblasts produce an excessive amount of
collagen in response to inflammatory mediators.” Id. “Cardiac fibroblasts
are the predominant source of synthesis of interstitial proteins and other
myocardial components which have been implicated in heart failure by their
effects on diastolic function and, indirectly, by effects on cardiac myocytes
to cause or potentiate systolic dysfunction.” Id.
3. Samuel discloses that “[a]cute ischemic damage to the heart is
associated with a progression to congestive heart failure.” Id. 13. “In
addition to the original damage, the process of remodelling results in an
even greater scarring response than necessary to mitigate the original
damage . . . [which] leads to a compensatory response in the remaining
tissue and an eventual hypertrophy and chronic failure.” Id.
4. Samuel discloses that “[cjhronic damage leading to
cardiomyopathy is also associated with heart failure. Cardiomyopathy
occurs when the heart becomes abnormally enlarged, thickened and/or
stiffened due to fibrosis.” Id. 14. “This condition . . . may be caused by a
wide range of conditions, including hypertension, chronic diseases,
alcoholism, viral diseases, and others.” Id. “[T]he fibrosis associated with
cardiomyopathies leads to a lessening in function of the tissue and decreased
contractility.” Id.
5. Samuel discloses “methods for treating diseases related to
cardiac fibrosis following either chronic or acute injury . . . [by]
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administering ... a pharmaceutical formulation comprising . . . relaxin
and/or an LGR7 activating agent to treat the resulting cardiac fibrosis.” Id.
110. “Reduction in fibrosis can be mediated by a decrease in fibroblast
activation, myofibroblast differentiation, collagen synthesis, collagen
deposition or matrix metal [ljoproteinase (MMP) expression. The effect of
relaxin and/or an LGR7 activating agent on these processes may be direct or
indirect.” Id.
6. Samuel discloses that
relaxin ... is delivered to a patient via systemic delivery. ... In
another embodiment, a therapeutically effective amount of
relaxin ... is delivered to a patient via local delivery. Local
delivery provides relaxin to the area of damage directly, and[] is
a more targeted method for reduction of fibrosis in a specific
area of injury. Examples of such delivery include . . .
administration via the use of a stenting device, administration
via a catheter . . . direct injection into or near the cardiac tissue,
[and] injection into the pericardium.
Id. 116.
7. Samuel further discloses an “association of fibrosis with the
heart failure process in a variety of heart diseases, including those associated
with both volume and pressure overload.” Id. f 54, “In the setting of heart
failure, fibrosis involves an increase in both fibroblast number and matrix
deposition . . . suggesting the importance of the fibroblast in the
development of this condition.” Id. “Cardiac fibroblasts are also the
predominant source of synthesis of interstitial proteins and other myocardial
components which have been implicated in heart failure by their effects on
diastolic function and, indirectly, by effects on cardiac myocytes to cause or
potentiate systolic dysfunction.” Id.
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8. Struijker-Boudier discloses compositions and methods that
provide “sustained-release of a drug to the heart or coronary vasculature
using an implanted dosage form that may be implanted in the cardiac or
vascular tissue.” Struijker-Boudier, If 70.
9. Struijker-Boudier discloses compositions and methods that
introduce “a cardiac drug into the pericardial space at a low volume and/or
low dosage rate.” Id. 11 89. “The methods are particularly useful for drug
delivery over an extended period of time for example, for delivery of drug at
a low volume rate to reduce the risk, incidence, and/or severity of adverse
side effects.” Id. “Introduction of the cardiac drug into the pericardial space
can be via transpericardial or intrapericardial routes.” Id.
10. Struijker-Boudier discloses that an “advantage of the methods
of the present invention is that relatively small quantities of a cardiac drug
can be administered over an extended period of time to the pericardial
space.” Id. “The methods . . . avoid the pitfalls associated with systemic
delivery of a cardiac drug, namely that high systemic doses are often
required to achieve an effective dose in the cardiac tissue . . . and such high
systemic doses may have deleterious effects on non-cardiac tissues.” Id.
Analysis
As an initial matter, we accept the Examiner’s finding that “it is
notoriously well known ... to diagnose a patient before treating them for a
disease.” See Fin. Rej. at 4; Ans. 6 (citing Samuel, H 49, 53, 117). With
respect to the cited art, the Examiner finds that Samuel discloses a method of
treating heart failure comprising the pericardial administration of an anti-
fibrotic agent such as relaxin. Ans. 2, citing Samuel, 116. The Examiner
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finds that Samuel does not disclose “identifying and treating heart failure
with preserved ejection faction specifically,” but “congestive heart failure
[CHF] is divisible into two types preserved vs reduced ejection fraction or
diastolic vs systolic heart failure and thus treating someone for CHF via the
method of Samuel will treat preserved ejection fraction heart failure.” Ans.
2. With respect to pericardial drug delivery, the Examiner finds that Samuel
“discloses using a local catheter” for heart failure treatment (Ans. 3, citing
Samuel, 116), whereas Struijker-Boudier “discloses treating both types of
CHF (systolic and diastolic . . .) via a local catheter . . . directly into the
pericardial space” (Ans. 3, citing Struijker-Boudier, || 89, 96, and 217).
The Examiner, thus, concludes that it would have been obvious to modify
Samuel’s method by “identifying and delivering the medication directly into
the pericardial space to treat either . . . type[] of CHF . . . [because] it is a
known . . . delivery method for cardiac drugs to treat CHF.” Ans. 3.
Appellants argue that claims 1 and 23 are directed “to methods of
treating heart failure with preserved ejection fraction . . . [and] include at
least two separate steps.” App. Br. 7. Appellants argue that, first, “a
determination is made that a subject suffers from heart failure with preserved
ejection fraction . . . [and] a second step involves the pericardial
administration of an anti-fibrotic agent... or relaxin.” App. Br. 7.
Appellants argue that “teachings of the generic treatment of chronic heart
failure . . . [do not] teach or make obvious the selection of a specific
subpopulation (those . . . with preserved ejection fraction)” for treatment.
App. Br. 9. Appellants argue that “[h]eart failure with preserved ejection
fraction and heart failure with reduced ejection fraction are separate and
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unique diseases that require individual treatment.” App. Br. 9. Appellants
argue that the combination of Samuel and Struijker-Boudier does not teach,
“first, the selection of a specific population of subjects (those suffering from
heart failure with preserved ejection fraction) and, second, the treatment of
this selected group of patients.” App. Br. 10.
Appellants’ arguments are not persuasive. The Specification discloses
that heart failure can be classified as either heart failure with preserved
ejection fraction (diastolic heart failure) or heart failure with reduced
ejection fraction (systolic heart failure). See the Spec, at 1:34—2:2. Samuel
discloses that relaxin and LGR7 can be used as anti-fibrotic agents to treat
diseases related to cardiac fibrosis such as congestive heart failure. FFs 1
and 5. Samuel discloses that one mechanism of action of relaxin or LGR7 is
an inhibition or decrease in fibroblast activation. FF 5. Samuel also
discloses that, in the context of heart failure, fibrosis involves an increase in
both fibroblast number and matrix deposition and that fibroblast activity is
associated with both diastolic and systolic heart failure. FF 7. Struijker-
Boudier teaches the benefits of pericardial drug administration of cardiac
drugs. FFs 9—10. Finally, as noted by the Examiner, it is well known to
diagnose a patient before treating them for a disease. See Ans. 6.
In view of the above, we agree with the Examiner that the
combination of Samuel with Struijker-Boudier would have made obvious
methods of treating heart failure by determining that a subject suffers from
heart failure with preserved ejection fraction, i.e. diastolic heart failure, and
then administering an anti-fibrotic agent, as required by claim 1, or
administering relaxin, as required by claim 23.
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Appellants argue that one of skill in the art would not have a
reasonable expectation of success in combining the teachings of Samuel and
Struijker-Boudier to arrive at the claimed methods of treating a subject with
heart failure with preserved ejection fraction. App. Br. 11. In particular,
Appellants argue that Filippatos5 * * * 9discloses “the effectiveness of relaxin
(‘serelaxin’) for the treatment of heart failure with preserved ejection
fraction (‘HFpEF’), which ‘is rather unique as several classes that represent
established therapies for HFrEF [heart failure with reduced ejection fraction]
failed to provide similar benefits in HFpEF [heart failure with preserved
ejection fraction]’.” App. Br. 12, citing Filippatos at 7—8.
We do not find Appellants’ arguments persuasive. Appellants
concede that Filippatos discloses that relaxin was effective for the treatment
of heart failure with preserved ejection fraction. Even if other therapies that
target heart failure with reduced ejection fraction are not effective at treating
heart failure with preserved ejection fraction, Filippatos’ express disclosure
that relaxin is effective rebuts previous results with other treatments.
Appellants argue that “a person of skill in the art would have no
common sense reason to modify the systemic delivery method of Samuel. . .
[with] the pericardial administration [method]” taught by Struijker-Boudier.
App. Br. 13. Appellants argue that Samuel discloses “that the preferred
method of delivery is ‘via systemic delivery’ and presents a number of
5 G. Filippatos et al., Serelaxin in acute heart failure patients with preserved
left ventricular ejection fraction: results from the RELAX-AHF trial, Eur.
Heart J. 35(16): 1041—1050 (April 2014), submitted with the Information
Disclosure Statement filed on February 12, 2014. App. Br. 12.
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advantages for using systemic delivery.” App. Br. 13—14, citing Samuel,
116. Appellants argue that Samuel’s disclosure
leaves the person of skill in the art with no reason to look for
alternative delivery methods and the disclosure of Samuel
would deter a person of skill in the art from attempting another
type of delivery method, in particular a method which is more
invasive and . . . [therefore] more expensive” and with more
risk for the patient.
App. Br. 14. Accordingly, Appellants argue, “a person of skill in the art
would not be motivated to alter the teachings of Samuel for pericardial
administration.” App. Br. 14.
Appellants’ arguments are not persuasive. Samuel discloses that
relaxin may be delivered to a patient via systemic or local delivery, and that
local delivery is a more targeted delivery method. FF 6. Samuel also
discloses that examples of local delivery include direct injection into or near
the cardiac tissue and injection into the pericardium. Id. Struijker-Boudier
discloses compositions and methods wherein cardiac drugs are introduced
into the pericardial space. FF 9. Struijker-Boudier discloses that the
methods are particularly useful for drug delivery over extended time periods
at a low volume rate, which reduces the risk, incidence, or severity of side
effects. FFs 9 and 10. In view of these disclosures, we agree with the
Examiner that the “pericardial administration of an anti-fibrotic agent,” as
required by claim 1, and that “the delivery of relaxin into the pericardial
space of the heart,” as required by claim 23, would have been obvious to one
of ordinary skill in the art for the purpose of avoiding side effects.
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Thus, we affirm the rejection of independent claims 1 and 23 under
35 U.S.C. § 103(a).6 * * * * 11Dependent claims 2—4, 6—10, 21, 22, and 24—35 have
not been argued separately and therefore fall with independent claims 1 and
23. See 37 C.F.R. § 41.37(c)(l)(iv).
Appellants also argue the rejection of claims 36 and 37. Claims 36
and 37 depend from independent claims 1 and 23, respectively, and further
require that “heart failure with preserved ejection fraction comprises an
ejection fraction of about 50 percent or greater.”
The Examiner finds that Samuel “does not disclose treatment if the
preserved ejection fraction comprises an ejection fraction of about 50
percent or greater.” Ans. 4. The Examiner concludes, however, that it
“would have been obvious to one of ordinary skill in the art... to determine
over which ranges the treatment is effective, since it has been held that
where the general conditions of a claim are disclosed in the prior art,
discovering the optimum or workable ranges involves only routine skill in
the art.” Ans. 4.
Appellants argue that the Examiner’s reasoning is in error because
“the combined teachings of Samuel and Struijker do not teach a method
including a step of determining that a subject suffers from heart failure with
preserved ejection fraction followed by the pericardial administration of an
anti-fibrotic agent. . . or relaxin.” App. Br. 17. Appellants argue that,
6 Appellants also present arguments directed to the Examiner’s citation of
the Toscano reference during prosecution (App. Br. 14—15). However, the
Examiner did not cite the Toscano reference in the statement of the rejection
and does not rely on Toscano’s disclosure in formulating the rejection.
Therefore, we do not further consider these arguments.
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therefore, “the general conditions of the claim have not been met and it
cannot be routine experimentation [to] discover optimal or workable
ranges.” App. Br. 17.
Appellants’ arguments are not persuasive for the reasons discussed
above. Thus, we affirm the rejection of claims 36 and 37 as being obvious
in view of Samuel and Struijker-Boudier.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
combination of Samuel and Struijker-Boudier would have made obvious a
method of treating a subject with heart failure with preserved ejection
fraction by the pericardial administration of an anti-fibrotic agent, as
required by claim 1, or relaxin, as required by claim 23.
SUMMARY
We affirm the rejection of claims 1—4, 6—10, and 21—37 under
35U.S.C. § 103(a).
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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